Fast answer
Choose Locorotondo when the trip is mainly an inland Valle d'Itria stay: white-town evenings, cummerse streets, countryside trulli, and short loops to Alberobello, Cisternino, or Martina Franca. Choose Monopoli when the fixed point is the coast, easier rail arrival, beach time, or a first Puglia base that needs more arrival infrastructure. The two towns can pair well, but they should not be treated as interchangeable overnight bases.
If you only do one thing
Default to Locorotondo for a car-led inland stay of white towns, trulli, and slow evenings. Default to Monopoli when sea access, beach days, rail convenience, or a broader first-arrival base matters more than sleeping in the Valle d'Itria.